Dynamic alterations of the extracellular matrix (ECM) is regarded as an important regulatory step in the development of cardiovascular diseases. This ECM remodeling initiates dysregulation of tissue homeostatsis and eventually induces tissue fibrosis, which results in functional and morphological deterioration of the heart and vessels. ECM remodeling is an important common pathological process in the development of heart failure, vascular restenosis after angioplasty, and pulmonary hypertension, which are all common clinical challenges seen in Pediatrics. Development of tissue fibrosis is a consequence of dysregulation of synthesis and degradation of the ECM. Fibulin-2 is a member of an emerging family of ECM proteins that is up-regulated during morphogenesis of cardiac valves and vessels and that is widely expressed in the vascular basement membrane post-natally. Our preliminary studies with Fibuln-2 deficient mice indicate that Fibulin-2 facilitates collagen deposition and thus myocardial fibrosis after experimental myocardial infarction. Here we propose to investigate regulation of ECM homeostasis in the development of cardiovascular diseases, heart failure and vascular remodeling, using Fibulin-2 deficient mouse model for altered ECM homeostasis. The central hypothesis of this proposal is that Fibulin-2 plays a crucial role in the )athogenesis of heart failure and in the development of vascular remodeling. We have two specific aims. Aim 1 focuses on the role of Fibulin-2 in the development of ventricular remodeling after permanent ischemic injury. For this, we will use both in vivo and in vitro models to determine role of Fibulin-2 in the pathogenesis of ventricular remodeling. Aim 2 focuses the role of Fibulin-2 in the development of vascular remodeling. For this, we will determine the role of Fibulin-2 in vascular remodeling in vivo in experimental models of systemic vascular injury and pulmonary hypertension.